It has been previously been shown by our lab and others that persistent organic pollutants, such as polychlorinated biphenyls (PCBs) and polybrominated diphenyl ethers (PBDEs), are contaminants in ...milk produced for human consumption. To further this research we determined the concentration of 21 PCB and 14 PBDE congeners in livestock serum, mainly bovine, across California. Congeners were extracted from serum using solid phase extraction (SPE), cleaned up by silica cartridge and quantified using gas chromatography-triple quadruple mass spectrometry. We detected significant differences among species and the production class of cattle (beef or dairy). The sum of all 21 PCB congeners (ΣPCBs) in caprine and ovine sera had a mean value of 9.26 and 9.13 ng/mL, respectively, compared to 3.98 ng/mL in bovine sera. The mean value for the sum of all 14 PBDE congeners (ΣPBDEs) in caprine and ovine sera was 2.82 and 2.39 ng/mL, respectively, compared to 0.91 ng/mL in bovine sera. Mean ΣPCBs in dairy cattle was 5.92 ng/mL compared to 2.70 ng/mL in beef cattle. Mean ΣPBDEs in dairy cattle was 1.33 ng/mL compared to 0.70 ng/mL in beef cattle. There were no regional differences in the ΣPCBs or ΣPBDEs in cattle distributed across California. These results highlight the fact that livestock are still being exposed to these pollutants yet little is known about where this exposure may be coming from.
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•Caprine and ovine sera contain higher levels of PCBs and PBDEs than sera of bovine.•Dairy cows have higher levels of PCBs and PBDEs than cows used in beef production.•A non-legacy PCB, PCB 11, was detected at quantifiable levels in all livestock sera.•There are no significant regional differences in the sum concentration of PCBs and PBDEs in bovine sera in California.
Canine Lymphomas Valli, V. E.; Kass, P. H.; Myint, M. San ...
Veterinary pathology,
09/2013, Letnik:
50, Številka:
5
Journal Article
Recenzirano
Canine lymphoma is the neoplasm most often treated by chemotherapy, yet there are few data to correlate response to therapy with its different subtypes. This study is based on biopsy specimens from ...992 dogs for which lymphoma was the clinical diagnosis. All cases were phenotyped by immunohistochemistry for CD3 and CD79alpha. Cases with histiocytic proliferation were evaluated immunohistochemically for CD18. Clonality was verified in 12 cases by polymerase chain reaction (PCR). Survival (event time) data and complete survival information (cause of death or time to last follow-up) were available on 456 dogs. Additional covariate information when available included size, age, sex, phenotype, stage and grade of lymphoma, mitotic index, and treatment protocol. Because of the many subtypes of B- and T-cell lymphoma, the cases were grouped into 7 diagnostic categories: (1) benign hyperplasia; (2) low-grade B-cell; (3) high-grade B- and T-cell; (4) low-grade T-cell; (5) centroblastic large B-cell of all mitotic grades (subdivided by clinical stage); (6) immunoblastic large B-cell of all mitotic grades, and (7) high-grade peripheral T-cell. Grouping was determined by histological grade (based on mitotic rate/400× field, with low-grade 0–5, intermediate 6–10, and high-grade >10) and stage for survival function estimation. No association with survival was found for size (based on breed of dog) or sex. All diagnostic categories of indolent or low-grade type had low mitotic rates, whereas those with clinically high grades had high mitotic rates. The diagnostic category with the most cases was centroblastic large B-cell lymphoma. Compared with dogs in this largest represented group of lymphomas, dogs with high-grade lymphomas had significantly higher mortality rates, and dogs with low-grade T-cell lymphomas had significantly lower mortality rates. Treatments for high-, intermediate-, and low-grade lymphomas were divided into 4 groups: absence of treatment, chemotherapy with or without hydroxydaunorubicin, and only prednisone. Dogs with low-grade T-cell (T-zone) lymphomas had the longest median survival (622 days), whereas the shortest median survival was in dogs with T-cell high-grade (peripheral T-cell) subtype (162 days). The dogs with centroblastic large B-cell lymphomas had a median survival of 127 days with low stage, 221 days with intermediate stage, and 215 days with advanced stage. Dogs with T-zone lymphoma were probably diagnosed in later stages of disease because of the lack of signs associated with progression. As with human lymphomas, a histological diagnosis with immunophenotyping is a minimal requirement for diagnosis of a specific subtype.
Feline Gastrointestinal Lymphoma Moore, P. F.; Rodriguez-Bertos, A.; Kass, P. H.
Veterinary pathology,
07/2012, Letnik:
49, Številka:
4
Journal Article
Recenzirano
Odprti dostop
Gastrointestinal lymphomas were identified in 120 cats between 1995 and 2006. Lymphomas were classified according to the World Health Organization (WHO) scheme. Cats with mucosal T-cell lymphoma (n = ...84) predominated and had a median survival of 29 months. Mucosal T-cell lymphoma matched WHO enteropathy-associated T-cell lymphoma (EATCL) type II. Epitheliotropic T-cell infiltrates were present in 62% of cats and occurred as clusters or diffuse infiltrates of small to intermediate-sized T cells in villous and/or crypt epithelium. Similar lymphocytes infiltrated the lamina propria in distinctive patterns. Cats with transmural T-cell lymphoma (n = 19) had a median survival of 1.5 months. Transmural T-cell lymphoma matched WHO EATCL type I. Epitheliotropic T-cell infiltrates were present in 58% of cats. Large lymphocytes (n = 11), mostly with cytoplasmic granules (LGL–granzyme B+) (n = 9) predominated. Transmural extension across the muscularis propria characterized the lesion. Both mucosal and transmural T-cell lymphomas were largely confined to the small intestine, and molecular clonality analysis revealed clonal or oligoclonal rearrangements of T-cell receptor-γ in 90% of cats. Cats with B-cell lymphoma (n = 19) had a median survival of 3.5 months. B-cell lymphomas occurred as transmural lesions in stomach, jejunum, and ileo–cecal–colic junction. The majority were diffuse, large B-cell lymphomas of centroblastic type. In conclusion, T-cell lymphomas characterized by distinctive mucosal architecture, CD3 expression, and clonal expansion predominated in the feline gastrointestinal tract.
A screening procedure for the identification of potential emerging chemical risks in the food and feed chain developed in a previous EFSA-sponsored pilot study was applied to 15021 substances ...registered under the REACH Regulation at the time of evaluation. Eligible substances were selected from this dataset by excluding (a) intermediates handled under strictly controlled conditions, (b) substances lacking crucial input data and (c) compounds considered to be outside the applicability domain of the models used. Selection of eligible substances resulted in a considerable reduction to 2336 substances. These substances were assessed and scored for environmental release (tonnage and use information from REACH registration dossiers), biodegradation (predictions from BIOWIN models 3, 5 and 6 evaluated in a battery approach), bioaccumulation in food/feed (ACC-HUMANsteady modelling) and chronic human health hazards (classification according to the CLP Regulation for carcinogenicity, mutagenicity, reproductive toxicity and repeated dose toxicity as well as IARC classification for carcinogenicity). Prioritisation based on the scores assigned and additional data curation steps identified 212 substances that are considered potential emerging risks in the food chain. Overall, 53% of these substances were prioritised due to chronic hazards identified in REACH registrations dossiers only (i.e. hazards not identified in classifications from other sources). Bioaccumulation in food and feed predicted on the basis of ACC-HUMANsteady modelling identified many substances that are not considered bioaccumulative in aquatic or terrestrial organisms based on screening criteria of the relevant ECHA guidance documents. Furthermore, 52% of the priority substances have not yet been assessed for their presence in food/feed by EU regulatory agencies. This finding and illustrative examples suggest that the screening procedure identified substances that have the potential to be emerging chemical risks in the food chain. Future research should investigate whether they actually represent emerging chemical risks as defined in EFSA's mandate.
The laboratory records from 384 dogs with a diagnosis of either melanoma or melanocytoma were selected for study. Significant negative determinants of patient survival for melanocytic tumors were: 1) ...metastasis, 2) mitotic index (MI), 3) nuclear atypia, 4) tumor score, 5) increasing size/volume, 6) the presence of deep inflammation, and/or 7) intralesional necrosis. In addition to these attributes, age was a significant determinant for tumors of the skin. For the feet and lips, 8) age and 9) junction activity negatively impacted survival. Mathematic models were constructed based on these significant determinants to predict the postsurgical outcome of melanocytic neoplasia. Melanocytic oral neoplasms comprised 19% (73/384) of the neoplasms; 92% of these were classified as malignant in the biopsy report, but malignant behavior (i.e., metastasis or recurrence) was observed in only 59% of cases. The prognostic model for oral tumors based on nuclear atypia provided the most accurate (89%) prediction of overall behavior. Melanocytic tumors of the feet and lips were also 19% (73/384) of the total population. Seventy-four percent were reported malignant, whereas only 38% actually demonstrated malignant behavior. The prognostic models based on both MI or nuclear atypia had an overall correct behavioral classification of 81%. Melanocytic tumors in the skin comprised 59% (227/384) of study specimens. Although 39% were reported as malignant, only 12% exhibited malignant behavior. A satisfactory predictive model that employed MI could not be constructed, but one using nuclear atypia gave an overall correct classification in 93.3% of the cases.
In humans, the drug metabolizing enzyme CYP2D6 is highly polymorphic resulting in substantial differences in the metabolism of drugs including anti-arrhythmics, neuroleptics, and opioids. The ...objective of this study was to phenotype a population of 100 horses from five different breeds and assess differences in the metabolic activity of the equine CYP2D6 homolog using codeine as a probe drug. Administration of a probe drug is a common method used for patient phenotyping in human medicine, whereby the ratio of parent drug to metabolite (metabolic ratio, MR) can be used to compare relative enzyme function between individuals. A single oral dose of codeine (0.6 mg/kg) was administered and plasma concentrations of codeine and its metabolites were determined using liquid chromatography mass spectrometry. The MR of codeine O-demethylation (codeine)/(morphine + morphine-3-glucuronide + morphine-6-glucuronide) was determined using the area under the plasma concentration-time curve extrapolated from time zero to infinity (AUC
) for each analyte and used to group horses into predicted phenotypes (high-, moderate-, and low-MR).
The MR of codeine O-demethylation ranged from 0.002 to 0.147 (median 0.018) among all horses. No significant difference in MR was observed between breeds, age, or sex. Of the 100 horses, 11 were classified as high-MR, 72 moderate-MR, and 17 low-MR. Codeine AUC
and O-demethylation MR were significantly different (p < 0.05) between all three groups. The mean ± SD MR was 0.089 ± 0.027, 0.022 ± 0.011, and 0.0095 ± 0.001 for high-, moderate-, and low-MR groups, respectively. The AUC for the morphine metabolites morphine-3-glucuronide and morphine-6-glucuronide were significantly different between high-and low-MR groups (p < 0.004 and p < 0.006).
The MR calculated from plasma following codeine administration allowed for classification of horses into metabolic phenotypes within a large population. The range of codeine metabolism observed among horses suggests the presence of genetic polymorphisms in CYP2D82 of which codeine is a known substrate. Additional studies including CYP2D82 genotyping of high- and low-MR individuals are necessary to determine the presence of CYP2D polymorphisms and their functional implications with respect to the metabolism of therapeutics.
BACKGROUND: A scoring system for outcome prediction in dogs with acute kidney injury (AKI) recently has been developed but has not been validated. HYPOTHESIS: The scoring system previously developed ...for outcome prediction will accurately predict outcome in a validation cohort of dogs with AKI managed with hemodialysis. ANIMALS: One hundred fifteen client‐owned dogs with AKI. METHODS: Medical records of dogs with AKI treated by hemodialysis between 2011 and 2015 were reviewed. Dogs were included only if all variables required to calculate the final predictive score were available, and the 30‐day outcome was known. A predictive score for 3 models was calculated for each dog. Logistic regression was used to evaluate the association of the final predictive score with each model's outcome. Receiver operating curve (ROC) analyses were performed to determine sensitivity and specificity for each model based on previously established cut‐off values. RESULTS: Higher scores for each model were associated with decreased survival probability (P < .001). Based on previously established cut‐off values, 3 models (models A, B, C) were associated with sensitivities/specificities of 73/75%, 71/80%, and 75/86%, respectively, and correctly classified 74–80% of the dogs. CONCLUSIONS AND CLINICAL RELEVANCE: All models were simple to apply and allowed outcome prediction that closely corresponded with actual outcome in an independent cohort. As expected, accuracies were slightly lower compared with those from the previously reported cohort used initially to develop the models.
BACKGROUND: Bronchiectasis is a permanent and debilitating sequel to chronic or severe airway injury, however, diseases associated with this condition are poorly defined. OBJECTIVE: To evaluate ...results of diagnostic tests used to document bronchiectasis and to characterize underlying or concurrent disease processes. ANIMALS: Eighty‐six dogs that had bronchoscopy performed and a diagnosis of bronchiectasis. METHODS: Retrospective case series. Radiographs, computed tomography, and bronchoscopic findings were evaluated for features of bronchiectasis. Clinical diagnoses of pneumonia (aspiration, interstitial, foreign body, other), eosinophilic bronchopneumopathy (EBP), and inflammatory airway disease (IAD) were made based on results of history, physical examination, and diagnostic testing, including bronchoalveolar lavage fluid analysis and microbiology. RESULTS: Bronchiectasis was diagnosed in 14% of dogs (86/621) that had bronchoscopy performed. Dogs ranged in age from 0.5 to 14 years with duration of signs from 3 days to 10 years. Bronchiectasis was documented during bronchoscopy in 79/86 dogs (92%), thoracic radiology in 50/83 dogs (60%), and CT in 34/34 dogs (100%). Concurrent airway collapse was detected during bronchoscopy in 50/86 dogs (58%), and focal or multifocal mucus plugging of segmental or subsegmental bronchi was found in 41/86 dogs (48%). Final diagnoses included pneumonia (45/86 dogs, 52%), EBP (10/86 dogs, 12%) and IAD (31/86 dogs, 36%). Bacteria were isolated in 24/86 cases (28%), with Streptococcus spp, Pasteurella spp, enteric organisms, and Stenotrophomonas isolated most frequently. CONCLUSIONS AND CLINICAL IMPORTANCE: Bronchiectasis can be anticipated in dogs with infectious or inflammatory respiratory disease. Advanced imaging and bronchoscopy are useful in making the diagnosis and identifying concurrent respiratory disease.
Central aortic pressures and waveform convey important information about cardiovascular status, but direct measurements are invasive. Peripheral pressures can be measured noninvasively, and although ...they often differ substantially from central pressures, they may be mathematically transformed to approximate the latter. We tested this approach, examining intersubject and intrasubject variability and the validity of using a single averaged transformation, which would enhance its applicability.
Invasive central aortic pressure by micromanometer and radial pressure by automated tonometry were measured in 20 patients at steady state and during hemodynamic transients (Valsalva maneuver, abdominal compression, nitroglycerin, or vena caval obstruction). For each patient, transfer functions (TFs) between aortic and radial pressures were calculated by parametric model and results averaged to yield individual TFs. A generalized TF was the average of individual functions. TFs varied among patients, with coefficients of variation for peak amplitude and frequency at peak amplitude of 24.9% and 16.9%, respectively. Intrapatient TF variance with altered loading (> 20% variation in peak amplitude) was observed in 28.5% of patients. Despite this, the generalized TF estimated central arterial pressures to < or = 0.2 +/- 3.8 mm Hg error, arterial compliance to 6 +/- 7% accuracy, and augmentation index to within -7% points (30 +/- 45% accuracy). Individual TFs were only marginally superior to the generalized TF for reconstructing central pressures.
Central aortic pressures can be accurately estimated from radial tonometry with the use of a generalized TF. The reconstructed waveform can provide arterial compliance estimates but may underestimate the augmentation index because the latter requires greater fidelity reproduction of the wave contour.
Background
Information regarding acute kidney injury (AKI) in cats is limited, and there are no reliable tools to objectively assess disease severity and predict outcome.
Objectives
To assess ...clinical signs, clinicopathologic abnormalities, etiology, and outcome of cats with AKI, and to develop models using clinical metrics and empirically derived scores to predict outcome.
Animals
One hundred and thirty‐two client‐owned cats.
Methods
Retrospective study. Bivariate logistic regression analyses were performed to identify variables predictive of 30‐day survival. Continuous variables outside the reference range were divided into quartiles to yield quartile‐specific odds ratios (OR) for survival. Models were developed incorporating weighting factors assigned to each quartile based on the OR. A predictive score for each model was calculated for each cat by summing all weighting factors. A second, multivariable logistic regression model was created from actual values of the same variables. Receiver operating characteristic curve analyses were performed to determine the models' performance. Models were further tested using a subset of cases not used in initial assessment.
Results
Fifty five of 132 cats (42%) remained dialysis‐independent for at least 30 days after discharge, and the remaining 77 cats either died (n = 37, 28%) or were euthanized (n = 40, 30%). The most common etiology was ureteral obstruction (n = 46, 35%). Higher scores were associated with decreased probability of survival (P < .001). Models correctly classified outcomes in 75–77% of the cases and 84–89% of the cases in the subsequent evaluation.
Conclusions and Clinical Importance
Models can provide objective guidance in assessing AKI prognosis and severity, but should be validated in other cohorts of cats.
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